Rapid cancer cell perineural invasion utilizes amoeboid migration Journal Article
| Authors: | Marcadis, A. R.; Kao, E.; Wang, Q.; Chen, C. H.; Gusain, L.; Powers, A.; Bakst, R. L.; Deborde, S.; Wong, R. J. |
| Article Title: | Rapid cancer cell perineural invasion utilizes amoeboid migration |
| Abstract: | The invasion of nerves by cancer cells, or perineural invasion (PNI), is potentiated by the nerve microenvironment and is associated with adverse clinical outcomes. However, the cancer cell characteristics that enable PNI are poorly defined. Here, we generated cell lines enriched for a rapid neuroinvasive phenotype by serially passaging pancreatic cancer cells in a murine sciatic nerve model of PNI. Cancer cells isolated from the leading edge of nerve invasion showed a progressively increasing nerve invasion velocity with higher passage number. Transcriptome analysis revealed an upregulation of proteins involving the plasma membrane, cell leading edge, and cell movement in the leading neuroinvasive cells. Leading cells progressively became round and blebbed, lost focal adhesions and filipodia, and transitioned from a mesenchymal to amoeboid phenotype. Leading cells acquired an increased ability to migrate through microchannel constrictions and associated more with dorsal root ganglia than nonleading cells. ROCK inhibition reverted leading cells from an amoeboid to mesenchymal phenotype, reduced migration through microchannel constrictions, reduced neurite association, and reduced PNI in a murine sciatic nerve model. Cancer cells with rapid PNI exhibit an amoeboid phenotype, highlighting the plasticity of cancer migration mode in enabling rapid nerve invasion. |
| Keywords: | genetics; pancreatic neoplasms; pancreas; mouse; animal; metabolism; animals; mice; cell motion; pancreas tumor; cell movement; neoplasm invasiveness; invasion; migration; tumor microenvironment; nervous tissue; sciatic nerve; nerve tissue; tumor invasion; amoeba; perineural; amoeboid; amoeba (life cycle stage) |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 120 |
| Issue: | 17 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2023-04-25 |
| Start Page: | e2210735120 |
| Language: | English |
| DOI: | 10.1073/pnas.2210735120 |
| PUBMED: | 37075074 |
| PROVIDER: | scopus |
| PMCID: | PMC10151474 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Richard J. Wong -- Source: Scopus |
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